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Enzyme-independent, orientation-selective conjugation of whole human complement C3 to protein surfaces

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Mitchell, Daniel Anthony, Ilyas, Rebecca, Dodds, Alister W. and Sim, Robert B.. (2008) Enzyme-independent, orientation-selective conjugation of whole human complement C3 to protein surfaces. Journal of Immunological Methods, Vol.337 (No.1). pp. 49-54. ISSN 0022-1759

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Official URL: http://dx.doi.org/10.1016/j.jim.2008.05.011

Abstract

Complement C3 is a central component of the humoral immune system. Upon triggering of the complement cascade, proteolytic fragments of C3 mediate important processes such as opsonization and lymphocyte activation. C3 possesses an internal thioester that mediates covalent attachment of proteolytically activated C3 to target surfaces. Treatment of native C3 with methylamine cleaves the thioester bond and exposes a free sulfhydryl group at the target-binding face of the protein. Through the use of sulfhydryl-reactive heterobifunctional Crosslinking and biotinylation reagents, we demonstrate the capacity to form stable, multimeric whole human C3-protein conjugates in a fashion reflecting the orientation of physiologically-activated C3. We speculate that this C3 conjugation strategy presents a route for targeting dendritic cells and macrophages. In addition, manipulation of the thioester bond could enhance the study of biological roles of C3 and related proteins such as C4, and also of transmissible agents that exploit complement function such as prions. (C) 2008 Elsevier B.V. All rights reserved.

Item Type:

Journal Article

Subjects:

Q Science > QD Chemistry
Q Science > QR Microbiology > QR180 Immunology

Divisions:

Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School

Library of Congress Subject Headings (LCSH):

Complement (Immunology), Immunological adjuvants, Biochemistry

Journal or Publication Title:

Journal of Immunological Methods

Publisher:

Elsevier BV

ISSN:

0022-1759

Official Date:

20 August 2008

Dates:

Date	Event
20 August 2008	Published

Volume:

Vol.337

Number:

No.1

Number of Pages:

Page Range:

pp. 49-54

Identification Number:

10.1016/j.jim.2008.05.011

Status:

Peer Reviewed

Publication Status:

Published

Access rights to Published version:

Restricted or Subscription Access

Funder:

European Union (EU), University of Warwick

Grant number:

FOOD-CT-2006-023144 (EU)

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